Current publicity about the health hazards of formaldehyde, recent changes in the rationale of pulp therapy for primary teeth, and a recognition of the detrimental properties of formocresol, challenges the dental profession to find an alternative pulpotomy agent. While formocresol enjoys the greatest clinical success of any current therapy, its drastic devitalization of tissue is universally acknowledged. Since the efficacy of formocresol is apparently derived from the protein-binding capacity of one of its components, formaldehyde, other agents with similar properties might be found which suitably fix the coronal tissue without jeopardizing the entire radicular pulp. Additionally, the ideal agent would achieve the fixation with little or no immunogenic alteration of protein, migrate negligibly from the tooth, and not localize in sites of mutagenic potential. In order to evaluate the degree and kind of fixation necessary for an effective pulpotomy medicament, we propose to compare two classes of protein-binding reagents to formaldehyde. These bifunctional reagents, glutaraldehyde and a diimidoester (dimethylsuberimidate) will be evaluated for their reactivity, cytotoxicity, capacity for metabolic suppression, their potential to create antigenic proteins from autologous tissue, and their pulpal and systemic distribution. Reactivity with pulp proteins will be compared by measuring the percentage of protein aggregated and made water-insoluble by intermolecular cross-links and by the resistance of fixed pulp to enzyme digestion in vitro. Cytotoxicity will be evaluated by a comparison of the recovery time required for the healing of connective tissue following chemical injury. Immunogenic potential will be explored by immunization of animals with treated proteins, by immunodiffusion assays, and by pulp response to treated homologous tissue placed in deep cavity preparations. Pulpal and systemic distribution and intracellular localizations following pulpotomies will be determined with isotopically labeled reagents using the technique of autoradiography, cell fractionation, and liquid scintillation spectroscopy.